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Hepatic First-Pass Metabolism

Meaning

Hepatic First-Pass Metabolism, or the first-pass effect, is a crucial pharmacokinetic phenomenon where the concentration of an orally administered drug is significantly reduced before it reaches the systemic circulation for distribution to target tissues. This profound reduction occurs because the compound, upon absorption from the gastrointestinal tract, is immediately transported via the portal vein directly to the liver, the body’s primary site of drug biotransformation. Liver enzymes, particularly the cytochrome P450 system, rapidly metabolize a portion of the active compound into inactive or less active metabolites, thereby lowering the drug’s effective bioavailability. This effect necessitates careful dosage adjustment or the use of alternative non-oral administration routes for many hormonal compounds.